期刊
OSTEOPOROSIS INTERNATIONAL
卷 31, 期 5, 页码 983-993出版社
SPRINGER LONDON LTD
DOI: 10.1007/s00198-019-05200-6
关键词
Immune therapy; Mutated RANKL; Osteoclast; Osteoporosis; RANK
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2018R1D1A1B07047024, 2017R1D1A3B03031764]
- National Research Foundation of Korea [2018R1D1A1B07047024, 2017R1D1A3B03031764] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment. Introduction Osteoclasts are responsible for bone resorption in bone-related disorders. Anti-cytokine therapeutic antibodies such as denosumab are effective for the treatment of osteoporosis. However, problems with antibody manufacturing and the immunogenicity caused by multiple antibody doses have led to the use of auto-cytokines as immunogens to induce anti-cytokine antibodies. Methods RANKL was point-mutated based on the crystal structure of the complex of RANKL and its receptor RANK. Results As a proof of concept, immunization with RANKL produced high levels of specific antibodies and blocked osteoclast development in vitro and inhibited osteoporosis in RANKL-treated or ovariectomized mouse models. Conclusions The results demonstrate the successful use of mutated RANKL as an immunogen for the induction of anti-RANKL immune response. This strategy is useful in general anti-cytokine immunotherapy to avoid toxic side effects of osteoporosis treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据